When compared with the adult, previous studies in young animals have shown a greater renal hypertrophic response following uninephrectomy (UN), which may involve formation of new nephrons. The functional correlates remain poorly understood, and are difficult to predict in view of the physiologic constraints of the immature kidney. The present study is designed to identify the nature and sequence of changes in single nephron and whole kidney function following UN and unilateral ureteral obstruction in the newborn guinea pig. After the animal has been anesthetized, micropuncture methodology will be used to measure proximal tubular, stop-flow, and peritubular capillary pressures, single nephron glomerular filtration rate, and fluid reabsorption. Clearance techniques will be used to measure kidney glomerular filtration and fractional sodium excretion. Arterial blood pressure will be monitored and renal blood flow will be measured with a flowmeter. These studies will be performed before and immediately after UN in the 1 day-old guinea pig as well as in a separate group examined at 3 weeks of age after UN at birth. The latter group will be compared with sham-operated animals of the same age. Studies of renal autoregulation and response to acute volume expansion will also be performed. The number of glomeruli in kidneys of each group will be estimated, and glomerular and proximal tubular volume will be determined by microdissection. Additional animals will undergo unilateral ureteral ligation during the first day of life in lieu of UN and will be similarly studied. The effect of UN on recovery from ischemia due to temporary renal artery occlusion in the newborn will be examined in 3 week-old animals following the same experimental approach. In contributing to an understanding of renal disease in early development, the results of this study will potentially lead to improved management of infants with congenital renal anomalies or perinatal circulatory insufficiency.